Fibroblasts for beauty and rejuvenation: soon in Russia!
The use of human fibroblasts is one of the most popular among cellular technologies in traumatology, kombustiology and aesthetic medicine.
Fibroblast (from "fibra" – "fiber", "blastos" – "sprout") is the most common and functionally significant cell of loose connective tissue. These cells belong to the mechanocyte line, have a round or elongated fusiform shape with processes and a flat oval nucleus, and are present in the stroma of all organs without exception. The main function of fibroblasts is to participate in the metabolism of intercellular matter. The condition and function of the main extracellular components of connective tissue, collagen, elastic and reticular fibers and intercellular matrix depend on the functional activity of fibroblasts. Fibroblasts synthesize and secrete a large number of biologically active substances into the surrounding space, among which various growth factors can be distinguished (EGF – epidermal growth factor, regulates the migration and proliferation of epidermal skin cells, FGF – fibroblast growth factor, stimulates the growth of all cell types and the production of extracellular matrix, KGF – keratinocyte growth factor, etc.), extracellular matrix components (glycosaminoglycans, hyaluronic acid, chondroitin sulfate) and enzymes. This process occurs continuously, and due to this, the intercellular substance is constantly being updated. The main sources of fibroblasts are the dermis of the skin and the postpartum placenta.
The dermis forms the basis of the skin, most of which is occupied by fibroblasts. Fibroblasts of the skin synthesize and secrete into the surrounding space a large amount of biologically active substances, extracellular matrix components and enzymes. This process occurs continuously, and due to this, the intercellular substance is constantly being updated.
With age, the thickness of the dermis decreases, the moisture content decreases, as a result, the skin loses elasticity and elasticity. As a result, wrinkles appear. Aging of the skin on various parts of the body proceeds unevenly. Open areas and skin in places of natural folds age especially quickly.
The number of fibroblasts in the skin also decreases with age, and they become less active. It is believed that one of the main causes of skin aging is a decrease in the ability of skin fibroblasts to divide and a decrease in the level of synthetic activity. Therefore, if these processes are stimulated in any way, it is possible to improve the condition of the skin. A wide variety of methods (peels, resurfacing, lifting, etc.) and drugs (botulinum toxin, extracellular matrix and connective tissue components, etc.) are currently used to correct age-related skin changes. Many of these methods are aimed at stimulating their own skin cells, in particular, fibroblasts. However, it is possible to solve the problem in another way – to increase the number of fibroblasts in the skin by transplanting them to those areas where it is necessary. The source of fibroblasts, in addition to the dermis of the skin, can be the postpartum placenta, the basis of the connective tissue layer of which (stroma rich in hyaluronic acid) are fibroblasts lying in a network of collagen and reticular fibers. Placental fibroblasts synthesize a complex of biologically active substances – growth factors, immunostimulators, enzymes and other active peptides that take an active part in the processes of cell activity (C. P. Chen, J. D. Aplin. Placental extracellular matrix: gene expression, deposition by placental fibroblasts and the effect of oxygen. Placenta. 2003, 24 (4), 316-325).
The principal possibility of using autologous (own) skin cells grown in vitro for wound healing was shown back in 1942 in the works of P. R. Medawar (Medawar P.R. The cultivation of adult mammalian skin epithelium in vitro // Quart.J.Microsc.Sci., 1948, 89 p.187-196). However, for a long time, researchers were unable to obtain enough cells to form a layer capable of replacing an autodermotransplant. Significant progress in this direction was achieved when they learned how to cultivate, that is, maintain the viability of fibroblasts outside the body (in vitro). In 1961, L. Hayflick and P.S.Moorhead presented data that even under optimal conditions of in vitro cultivation, human fibroblasts are able to divide only a limited number of times, 50+/-10 (L. Hayflick, P.S. Moorhead. The serial cultivation of human diploid cell strains. Exp. Cell Res. 1961; 25, 585-621. L. Hayflick. The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research. 1965, 37, 614-636). This phenomenon was called the "Hayflick limit". Later, various methods of isolating and culturing cells from the dermis of the skin were developed.
It has been shown that fibroblasts in culture retain a diploid karyotype, are able to grow only in a state attached to the surface of the culture vial, possess the phenomenon of contact inhibition, synthesize proteoglycans and have a limited lifespan (R.T. Dell'Orco. The use of arrested populations of human diploid fibroblasts for the study of senescence in vitro. Adv Exp Med Biol. 1975, 53, 41-9. L. Hayflick. The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research. 1965, 37, 614-636. I.A. Schafer et al. Isolation and preliminary characterization of proteoglycan aggregates from cultured dermal fibroblasts. J. Biol. Chemistry. 1984. 259, 2321-2330.). In addition, they are not oncogenic and have low expression of histocompatibility antigens. These features of fibroblasts were fixed in the form of methodological guidelines, which all obtained fibroblast cultures must comply with (Guidelines RD 42-28-10-89, Ministry of Health of the USSR, Moscow 1989). If these requirements are met, it became possible to use human fibroblasts cultivated outside the body for the production of immunobiological medicines, and then for therapeutic purposes.
In world practice, auto- and allogeneic fibroblasts were initially used in the treatment of burns in the treatment of burns, and later began to be used in aesthetic medicine.
Data from a number of researchers from different countries and Russian scientists suggest that technologies using proprietary skin fibroblasts are safe and effective in correcting age-related skin changes and treating post-acne scars. Currently, both own and donor skin fibroblasts are used for therapeutic purposes.
In 2000, American scientists presented the results of limited clinical studies on the use of their own dermal fibroblasts for the correction of facial soft tissue defects. The researchers observed a significant persistent clinical effect in patients with the correction of wrinkles, nasolabial folds and post-acne scars after intradermal administration of their own dermal fibroblasts. The injected fibroblasts synthesized a large amount of collagen, the main structural component of the skin. Researchers have shown that cultured skin fibroblasts obtained even from patients aged 60-61 years do not lose their ability to multiply and produce collagen. From 2003 to 2008, the American company Isolagen conducted international FDA clinical trials on the use of its own dermal fibroblasts for the correction of skin defects, including wrinkles and folds, in which more than 800 patients participated. The main objective of the research is to study the safety and clinical efficacy of the use of proprietary dermal fibroblasts for the correction of skin defects. Fibroblasts were injected intradermally, three times, with an interval between procedures of 1-6 weeks. The results of the studies demonstrated a significant reduction of wrinkles and improvement of the skin condition. The clinical effect is gradually increasing and persisting for at least a year. It was concluded that the technology of using proprietary dermal fibroblasts to correct skin defects is a new treatment method based on a unique biological mechanism that allows achieving a long–term clinical result, and the technology itself is safe and effective.
It should also be noted that this technology allows you to "bank" the patient's own skin fibroblasts, which makes it possible to use "banked" cells at any time if necessary. It is known that the lifetime of fibroblasts is limited, and, accordingly, skin fibroblasts obtained from a patient at a younger age are clinically more effective. Therefore, it is interesting to create a bank of skin fibroblasts taken from patients at a younger age, so that later, if necessary, their own cells with high functional potential can be transplanted to them in adulthood. Such "banking" of the skin's own fibroblasts is a kind of "biological insurance" of a person.
Russian researchers are not lagging behind their Western colleagues in introducing the achievements of world science in the field of cellular technologies related to fibroblasts. It is obvious that global innovations in aesthetic medicine will soon be available in Russia.
In the review "Dermal fibroblasts: what's new? Prospects of clinical application", published in the journal "Cosmetics and Medicine" No. 3-2010, in particular, the most promising domestic developments in the field of fibroblasts in aesthetic medicine are listed.
So, on the basis of the Faculty of Fundamental Medicine of Lomonosov Moscow State University, studies were conducted that demonstrated the biological safety and effectiveness of using human dermal fibroblasts to improve the condition of the skin.
On the basis of the Samara State Medical University and the cosmetology department of the Beauty Institute LLC (Samara), clinical studies were conducted on the use of own skin fibroblasts for the correction of post-acne scars. The results of the studies have shown that intradermal transplantation of own skin fibroblasts in patients with post-acne scars can significantly improve the results of treatment compared with traditional therapy. Clinical studies on the use of proprietary dermal fibroblasts for the correction of age-related skin changes were also conducted at the bases of the Ural State Medical Academy, the Middle Ural Scientific Center of the Russian Academy of Medical Sciences and the Institute of Medical Cell Technologies. Observations of the results of the use of own skin fibroblasts were carried out for two years. The effect was of an increasing nature, reached a maximum 15 months after the introduction of cells and persisted for at least 2 years. There were no complications after intradermal injection of own dermal fibroblasts during the follow-up period.
Clinical studies within the framework of the intersectoral program "New Cell Technologies-Medicine" were conducted on the basis of the Russian State Medical University and the V.N. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences. The purpose of these studies was to study the safety and effectiveness of the use of cultured own dermal fibroblasts for the correction of age-related skin changes. After the introduction of fibroblasts, there was a decrease in wrinkles, an increase in elasticity and microcirculation of the skin, an increase in its thickness. The clinical effect was increasing and persisted for at least 8-12 months. According to the results of the conducted studies, the authors concluded that the use of cultured own dermal fibroblasts for the correction of age-related skin changes is safe and effective.
Perhaps one of the first in Russia in this field will be the Human Stem Cell Institute, which is already preparing for the commercial launch of SPRS therapy - a comprehensive service for individual skin regeneration based on a registered technology for correcting skin defects using autologous skin fibroblasts.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Center for Cell Research and the website stem-cells.ru
29.10.2010